N,N-bis(N'-Fmoc-3-aminopropyl)glycine potassium hemisulfate | 346694-76-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N,N-bis(N'-Fmoc-3-aminopropyl)glycine potassium hemisulfate
• 英文别名: 12-Oxa-2,6,10-triazatridecanoic acid, 6-(carboxymethyl)-13-(9H-fluoren-9-yl)-11-oxo-, 1-(9H-fluoren-9-ylmethyl) ester, potassium salt, sulfate；potassium;2-[bis[3-(9H-fluoren-9-ylmethoxycarbonylamino)propyl]amino]acetate;sulfuric acid
• CAS: 346694-76-6
• 化学式: C₃₈H₃₉N₃O₆*HO₄S*K
• 分子量: 769.914
• InChiKey: UJLDYJZWBMMNRT-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  53
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  203
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N,N-bis(N'-Fmoc-3-aminopropyl)glycine potassium hemisulfate 、 在 N-甲基吗啉 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Biotin Derivatives Carrying Two Chelating DOTA Units. Synthesis, in Vitro Evaluation of Biotinidases Resistance, Avidin Binding, and Radiolabeling Tests

  摘要：

  The synthesis of four biotin derivatives carrying two DOTA moieties for each ligand (BisDOTA set) is reported, for increasing radiation/dose ratio and improving efficiency in the pretargeted avidin-biotin radioimmunotherapy. The biotin-containing scaffold of two BisDOTA was similar to the mono-DOTA derivative previously described. Then the scaffold was elongated by trifunctionalized spacers of different length and conjugated with one of the COOH groups of two DOTA. Two others were prepared starting from a on-resin lysine residue. The lysine alpha-NH2 was bonded to blotin, and then spacers were appended to the alpha-NH2 and conjugated with two DOTA molecules. One compound contairted a p-aminoberizoic acid spacer, which ensured higher head-to-tail distance and increased rigidity ofthe chain. These last two compounds had a very high ability to bond avidin and were labeled with Y-90 at high specific activity. All the compOLInds were resistant to the action of'scrurn biotinidases.

  DOI：

  10.1021/jm9014372

文献信息

• Design, Synthesis, In Vitro and In Vivo Evaluation of Heterobivalent SiFAlin-Modified Peptidic Radioligands Targeting Both Integrin αvβ3 and the MC1 Receptor—Suitable for the Specific Visualization of Melanomas?
  作者：Xia Cheng、Ralph Hübner、Valeska von Kiedrowski、Gert Fricker、Ralf Schirrmacher、Carmen Wängler、Björn Wängler

  DOI：10.3390/ph14060547

  日期：——

  tumor-to-background ratios than [18F]2. Thus, [18F]4 demonstrates to be a highly potent radiotracer for the sensitive and bispecific imaging of malignant melanoma by PET/CT imaging and impressively illustrates the suitability of the underlying concept to develop heterobivalent integrin αvβ3- and MC1R-bispecific radioligands for the sensitive and specific imaging of malignant melanoma by PET/CT.

  与单价肽配体相比，将针对两种不同受体的两种肽结合到异二价肽配体 (HBPL) 被认为能够提高肿瘤靶向敏感性，从而提高肿瘤可视化。在黑色素瘤的情况下，黑皮质素 1 受体 (MC1R)，在大多数原发性恶性黑色素瘤中稳定过表达，以及整合素 α v β 3参与淋巴结转移，因此在从局部疾病到转移性疾病的转变中具有重要作用，是重要的靶受体。因此，如果能够开发出能够与两种受体类型结合的放射性标记的 HBPL，那么疾病的早期诊断和正确分期将显着增加。在这里，我们报告了不同 SiFA lin修饰的 HBPL（SiFA = 氟化硅受体）的设计、合成、放射性标记以及体外和体内测试，包括 MC1R 靶向（GG-Nle-c（DHfRWK））和整合素 α v β 3 -亲和肽 (c(RGDfK))，通过对称分支框架连接，包括不同长度和组成的接头。套件式18HBPL 1 – 6 的F 放射性标记提供了标记产品 [ 18
• INHIBITION OF DRUG BINDING TO SERUM ALBUMIN
  申请人：Bitonti J. Alan

  公开号：US20050037947A1

  公开（公告）日：2005-02-17

  The invention relates to improved therapeutics for treating diseases or conditions that provide greater bioavailabilty and more predictable dosing. The invention relates to a chimeric protein comprised of a biologically active molecule linked to an Fc fragment of an immunoglobulin, wherein the chimeric protein binds less serum albumin compared to the same biologically active molecule of the chimeric protein not linked to an Fc fragment of an immunoglobulin. The invention also relates to a method of treating a disease or condition said method comprising administering a chimeric protein comprising a biologically active molecule linked to an Fc fragment of an immunoglobulin, wherein the chimeric protein binds less serum albumin compared to the same biologically active molecule of the chimeric protein not linked to an Fc fragment of an immunoglobulin

  本发明涉及改进的治疗方法，用于治疗提供更高生物利用度和更可预测剂量的疾病或病况。本发明涉及一种嵌合蛋白，包括生物活性分子和免疫球蛋白Fc片段，其中该嵌合蛋白与相同的未连接免疫球蛋白Fc片段的生物活性分子相比，结合较少的血清白蛋白。本发明还涉及一种治疗疾病或病况的方法，包括给予一种嵌合蛋白，该嵌合蛋白包括生物活性分子和免疫球蛋白Fc片段，其中该嵌合蛋白与相同的未连接免疫球蛋白Fc片段的生物活性分子相比，结合较少的血清白蛋白。
• Effects of Lysine N-ζ-Methylation in Ultrashort Tetrabasic Lipopeptides (UTBLPs) on the Potentiation of Rifampicin, Novobiocin, and Niclosamide in Gram-Negative Bacteria
  作者：Linus Schweizer、Danyel Ramirez、Frank Schweizer

  DOI：10.3390/antibiotics11030335

  日期：——

  Outer membrane (OM) drug impermeability typically associated with a molecular weight above 600 Da and high hydrophobicity prevents accumulation of many antibiotics in Gram-negative bacteria (GNB). Previous studies have shown that ultrashort tetrabasic lipopeptides (UTBLPs) containing multiple lysine residues potentiate Gram-positive bacteria (GPB)-selective antibiotics in GNB by enhancing OM permeability. However, there is no available information on how N-substitution at the ζ-position of lysine in UTBLPs affects antibiotic potentiation in GNB. To study these effects, we prepared a series of branched and linear UTBLPs that differ in the degree of N-ζ-methylation and studied their potentiating effects with GPB-selective antibiotics including rifampicin, novobiocin, niclosamide, and chloramphenicol against wild-type and multidrug-resistant GNB isolates. Our results show that increasing N-ζ-methylation reduces or abolishes the potentiating effects of UTBLPs with rifampicin, novobiocin, and niclosamide against GNB. No trend was observed with chloramphenicol that is largely affected by efflux. We were unable to observe a correlation between the strength of the antibiotic potentiating effect to the increase in fluorescence in the 1-N-phenylnaphthylamine (NPN) OM permeability assay suggesting that other factors besides OM permeability of NPN play a role in antibiotic potentiation. In conclusion, our study has elucidated crucial structure–activity relationships for the optimization of polybasic antibiotic potentiators in GNB.

  外膜药物不透过性通常与分子量大于600 Da和高亲水性有关，这防止了许多抗生素在革兰氏阴性菌中的积累。以前的研究表明，含有多个赖氨酸残基的超短四碱基脂肽（UTBLPs）通过增强外膜渗透性，增强了革兰氏阳性菌（GPB）选择性抗生素对革兰氏阴性菌（GNB）的作用。然而，目前没有关于UTBLPs中赖氨酸N-ζ位取代如何影响GNB中抗生素增强作用的信息。为了研究这些影响，我们制备了一系列分支和线性UTBLPs，它们在N-ζ-甲基化程度上有所不同，并研究了它们与包括利福平、诺伐菌素、尼克洛酰胺和氯霉素在内的GPB选择性抗生素对野生型和多重耐药GNB分离株的增强效应。我们的结果表明，增加N-ζ甲基化降低或消除了UTBLPs与利福平、诺伐菌素和尼克洛酰胺对GNB的增强作用。对于受外流影响较大的氯霉素，没有观察到任何趋势。我们无法观察到抗生素增强效应的强度与1-N-苯基萘胺（NPN）外膜渗透性测定中荧光增加的相关性，这表明除了NPN的外膜渗透性外，其他因素在抗生素增强中也起着作用。总之，我们的研究阐明了优化GNB中多碱基抗生素增强剂的关键结构-活性关系。
• Dilipid Ultrashort Tetrabasic Peptidomimetics Potentiate Novobiocin and Rifampicin Against Multidrug-Resistant Gram-Negative Bacteria
  作者：Danyel Ramirez、Liam Berry、Ronald Domalaon、Marc Brizuela、Frank Schweizer

  DOI：10.1021/acsinfecdis.0c00017

  日期：2020.6.12

  The development of new antibacterial agents and therapeutic approaches is of high importance to address the global problem of antibiotic resistance. Although antimicrobial peptides are known to synergize with certain antibiotics, their clinical application is limited by their systemic toxicity, protease instability, and high production cost. To overcome these problems, nine dilipid ultrashort tetrabasic peptidomimetics (dUSTBPs) were prepared consisting of three basic amino acids separated by a molecular scaffold, bis(3-aminopropyl)glycine, and were ligated to two fatty acids. Several nonhemolytic dUSTBPs were shown to enhance the activity of several antibiotics against pathogenic Gram-negative bacteria. More importantly, dUSTBP 8, consisting of three L-arginine units and a dilipid of 8 carbons long, potentiated novobiocin and rifampicin consistently against multidrug-resistant (MDR) clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. Preliminary studies suggested that dUSTBPs were likely to potentiate antibiotics through outer membrane permeabilization and/or disruption of active efflux and that dUSTBP 8 exhibited enhanced resistance to trypsin in comparison to the previously described di-C-9-KKKK-NH2 antibiotic potentiator. The antibacterial activity of rifampicin and novobiocin was enhanced by dUSTBP 8 comparable to other known outer membrane permeabilizing potentiators including the gold standard polymyxin B nonapeptide. Our results indicate that ultrashort tetrabasic peptidomimetics are potent adjuvants that repurpose novobiocin and rifampicin as potent agents against priority MDR Gram-negative pathogens.
• WO2007/39437
  申请人：——

  公开号：——

  公开（公告）日：——